Cardiac arrhythmias may occur in more than 60% of patients undergoing anesthesia and surgery, yet their mechanisms within this context remain obscure. Supraventricular rhythm disturbances are most common. If these are bradycardia, tachycardia, or interfere with atrial transport function, they may cause circulatory impairment or lead to more dangerous ventricular arrhythmias. The focus of this investigation, therefore, will be to determine mechanisms for supraventricular arrhythmias during anesthesia. It is suggested that anesthetic drugs alone, through interactions with other drugs and altered physiologic states, or due to autonomic-mediated effects, may interfere with normal relationships between primary (sinus node) and secondary (subsidiary atrial, atrial ectopic, AV junctional) pacemakers of the heart. This action, combined with previously described and largely depressant effects of the anesthetics on supraventricular conduction and refractoriness, would be the cause for ectopic atrial and AV junctional rhythm disorders. Circulatory disturbances secondary to these, especially with autonomic imbalance or increased endogenous catecholamines due to the stress of surgery, could lead to more dangerous ventricular arrhythmias. These hypotheses will be tested employing in vivo and in vitro canine models under three specific aims: The first aim will be to test anesthetic drug effects in chronically instrumented dogs with subsidiary pacemaker rhythms produced by surgical excision of the sinus node, with or without adjacent tissue along the sulcus terminalis (location of subsidiary atrial pacemakers). The second aim will be to test anesthetic drug effects on pacemaker location, automaticity and stability utilizing an in vitro canine perfused right atrial preparation. The third aim will be to determine cellular mechanisms for anesthetic drug effects observed above by utilizing intracellular recording from documented sites of primary and secondary pacemaker activity. The results of the planned investigation should further our understanding of mechanisms for common and sometimes troublesome arrhythmia, which can only lead to their more effective prevention and management in patients undergoing anesthesia and surgery. Additionally, results of this investigation should have relevance for the management of patients with sinus node dysfunction and heart block.